ClinVar Genomic variation as it relates to human health
NM_000152.5(GAA):c.172C>T (p.Gln58Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000152.5(GAA):c.172C>T (p.Gln58Ter)
Variation ID: 188903 Accession: VCV000188903.17
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q25.3 17: 80104758 (GRCh38) [ NCBI UCSC ] 17: 78078557 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 29, 2015 Feb 14, 2024 Apr 20, 2020 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000152.5(GAA):c.172C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000152.5:c.172C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000143.2:p.Gln58Ter nonsense NM_001079803.3:c.172C>T NP_001073271.1:p.Gln58Ter nonsense NM_001079804.3:c.172C>T NP_001073272.1:p.Gln58Ter nonsense NC_000017.11:g.80104758C>T NC_000017.10:g.78078557C>T NG_009822.1:g.8203C>T LRG_673:g.8203C>T LRG_673t1:c.172C>T - Protein change
- Q58*
- Other names
- -
- Canonical SPDI
- NC_000017.11:80104757:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00020 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
GAA | - | - |
GRCh38 GRCh38 GRCh37 |
2757 | 2807 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (4) |
reviewed by expert panel
|
Apr 20, 2020 | RCV000169263.13 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Apr 20, 2020)
|
reviewed by expert panel
Method: curation
|
Glycogen storage disease, type II
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel
Accession: SCV001371756.1
First in ClinVar: Jul 16, 2020 Last updated: Jul 16, 2020 |
Comment:
This variant, c.172C>T (p.Gln58Ter), is a nonsense variant, predicted to result in nonsense-mediated decay and lack of gene product, meeting PVS1. The variant is not … (more)
This variant, c.172C>T (p.Gln58Ter), is a nonsense variant, predicted to result in nonsense-mediated decay and lack of gene product, meeting PVS1. The variant is not in gnomAD v2.1.1, meeting PM2. This variant was found in compound heterozygosity with a pathogenic variant in two patients who meet the ClinGen LSD VCEP's PP4 specifications; one with c.525delT, confirmed in trans (PMID 10377006), and the other with c.841C>T (p.Arg281Trp), identified in a clinical diagnostic laboratory. This data meets PM3. Of note, pseudodeficiency variants are absent in the latter patient, allowing PP4_Moderate to be applied. Additional patients have been reported but were not included because the residual GAA activity was not provided and therefore PP4 cannot be assessed (PMID 20817528). There is a ClinVar entry for this variant (Variation ID: 188903, 1 star review status) with one submitter classifying the variant as likely pathogenic. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM2, PM3, PP4_Moderate. (less)
|
|
Likely pathogenic
(Jul 25, 2014)
|
criteria provided, single submitter
Method: literature only
|
Glycogen storage disease, type II
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220554.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
Pathogenic
(Aug 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Glycogen storage disease, type II
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001410342.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 188903). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 188903). This premature translational stop signal has been observed in individual(s) with glycogen storage disease (PMID: 10377006). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln58*) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). (less)
|
|
Pathogenic
(Jun 06, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Glycogen storage disease type II
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002091890.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience. | Bali DS | American journal of medical genetics. Part C, Seminars in medical genetics | 2012 | PMID: 22252923 |
Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study. | van Capelle CI | Neuromuscular disorders : NMD | 2010 | PMID: 20817528 |
Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. | Kroos M | Human mutation | 2008 | PMID: 18425781 |
Increased occurrence of cleft lip in glycogen storage disease type II (GSDII): exclusion of a contiguous gene syndrome in two patients by presence of intragenic mutations including a novel nonsense mutation Gln58Stop. | Huie ML | American journal of medical genetics | 1999 | PMID: 10377006 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/754c7592-35d5-41bd-83e3-3babcec0b5d8 | - | - | - | - |
Text-mined citations for rs201185475 ...
HelpRecord last updated Feb 14, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.